The general purpose of the proposed research is to study the genetic basis for enterotoxin production in epidemic strains of Escherichia coli and Vibrio comma. The major premise of the research is that the capacity of enteric organisms to elaborate enterotoxin is associated, in a significant proportion of instances, with accessory elements called plasmids. A simple method for detecting enterotoxin plasmids, ent, has been developed and has already been applied to human isolates with some success. Additionally, it has been demonstrated that Vibrio comma plasmids can be detected by the method. Support is requested to extend these findings and to define more precisely the genetic and molecular basis of enterotoxin production. Plasmids bearing the ent property will be transferred into enteric species with well- defined genetic backgrounds. These converted strains will be tested in an animal-model to not only determine the role enterotoxin plays in enteric disease but also to discover other necessary genetic properties of the bacterial host which are necessary to accomplish a successful infection. Most cases of acute gastroenteritis are generally not associated with any known bacterial or viral pathogen. Several lines of investigation have incriminated members of the "normal" intestinal flora as the culprits. The research proposed here attempts to define one basis for the capacity of these microorganisms to cause disease and to define ways for the development of preventive measures.